Moxibustion Enhances Ovarian Function by Inhibiting the Th17/IL‐17 Pathway and Regulating Gut Microbiota in POI Rats

PROBLEM: Premature ovarian insufficiency (POI) is a significant cause of female infertility, severely impacting physical and mental health. Current treatments, primarily hormone replacement therapy, fail to restore ovarian function and may cause adverse effects. Moxibustion, a traditional Chinese medicine therapy, has shown potential in treating POI, but its mechanisms remain unclear. This study investigated the therapeutic effects of moxibustion on POI rats and explored its underlying mechanisms. METHOD OF STUDY: A POI rat model was established using cyclophosphamide, and moxibustion was applied daily to the CV4 and SP6 acupoints for 4 weeks. We analyzed hormone levels, estrous cycles, follicle count, and gut microbiota. Transcriptomic and metagenomic sequencing were performed to identify potential pathways. Network pharmacology was used to predict active components and targets. RESULTS: Moxibustion restored estrous cycles, improved hormonal imbalances, and increased ovarian reserve function. Network pharmacology identified five active components in moxa, and based on the results of network pharmacology and transcriptome sequencing, we believe that the regulation of the IL-17 pathway is the key mechanism. Further experiments showed moxibustion downregulated the Th17/IL-17 pathway, reduced key proteins such as IL-17R, NF-κB, MMP3, IκBα, IL-1β, MMP9, TRAF6, and Cox2. Flow cytometry confirmed a decrease in Th17 cell proportion. Gut microbiota analysis revealed that moxibustion enhanced microbial diversity and modulated specific bacterial species, which correlated with improved hormone levels. CONCLUSION: Moxibustion has a therapeutic effect on POI rats by regulating the Th17/IL17 pathway and gut microbiota, which provides evidence for the clinical application of moxibustion.